The goal of this research proposal is to develop endoscope compatible, fluorescence spectroscopy systems for real time detection of precancerous alterations in colonic mucosa and urinary bladder wall. Both fiber optic-based contact probe techniques for localized detection and fluorescence spectral endoscope systems for wide area imaging of disease will be developed and applied clinically. Multi-wavelength excitation fluorescence and reflectance system will be used to characterize the optical/spectroscopic properties of relevant tissue types. The results of this study will be used to select optimal excitation wavelength(s) and design fiber probes with controllable sampling depth for targeting detection of superficial lesions. Microfluorimetry and fluorescence microscopic imaging will be used to identify fluorophores in cells and other morphological structures. By combining this information with tissue optical parameters, models of colon and bladder fluorescence measured at colonoscopy and cystoscopy respectively, will be developed. Inverse modeling will be developed for extracting histopathological information from the clinical spectra. Fluorescence spectral imaging cystoscope will be developed for urinary bladder studies, and the existing fluorescence imaging colonoscope will be modified for colon studies. The techniques developed in this program will be clinically tested for rapid detection of colorectal dysplasia/carcinoma in chronic ulcerative colitis and other settings, and dysplasia/transitional cell carcinoma in the urinary bladder.